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Breast Cancer Research and Treatment

, Volume 172, Issue 2, pp 339–351 | Cite as

Somatic EP300-G211S mutations are associated with overall somatic mutational patterns and breast cancer specific survival in triple-negative breast cancer

  • Vahid Bemanian
  • John Christopher Noone
  • Torill Sauer
  • Joel Touma
  • Katja Vetvik
  • Cecilia Søderberg-Naucler
  • Jonas Christoffer Lindstrøm
  • Ida Rashida Bukholm
  • Vessela N. Kristensen
  • Jürgen Geisler
Preclinical study
  • 129 Downloads

Abstract

Purpose

We have compared the mutational profiles of human breast cancer tumor samples belonging to all major subgroups with special emphasis on triple-negative breast cancer (TNBC). Our major goal was to identify specific mutations that could be potentially used for clinical decision making in TNBC patients.

Patients and methods

Primary tumor specimens from 149 Norwegian breast cancer patients were available. We analyzed the tissue samples for somatic mutations in 44 relevant breast cancer genes by targeted next-generation sequencing. As a second confirmatory technique, we performed pyrosequencing on selected samples.

Results

We observed a distinct subgroup of TNBC patients, characterized by an almost completely lack of pathogenic somatic mutations. A point mutation in the adenoviral E1A binding protein p300 (EP300-G211S) was significantly correlated to this TNBC subgroup. The EP300-G211S mutation was exclusively found in the TNBC patients and its presence reduced the chance for other pathological somatic mutations in typical breast cancer genes investigated in our gene panel by 94.9% (P < 0.005). Interestingly, the EP300-G211S mutation also predicted a lower risk for relapses and decreased breast cancer-specific mortality during long-term follow-up of the patients.

Conclusion

Next-generation sequencing revealed specific mutations in EP300 to be associated with the mutational patterns in typical breast cancer genes and long-term outcome of triple-negative breast cancer patients.

Keywords

Breast cancer EP300 mutations Triple-negative breast cancer TP53 Next-generation sequencing Pyrosequencing 

Notes

Acknowledgements

The authors thanksfully acknowledge Ms. Gro Gundersen, Ms. Eva Smedsrud and M.Sc. Torben Lüders for the preparation of genomic DNA from FFPE samples (G.G. & E.S.) and EDTA-samples prior to pyrosequencing (T.L.).

Funding

This study was funded by Bodil and Magne´s Cancer Research Fund, Oslo, Norway.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Vahid Bemanian
    • 1
  • John Christopher Noone
    • 1
  • Torill Sauer
    • 2
    • 3
  • Joel Touma
    • 4
    • 5
  • Katja Vetvik
    • 3
    • 4
  • Cecilia Søderberg-Naucler
    • 6
  • Jonas Christoffer Lindstrøm
    • 3
    • 7
  • Ida Rashida Bukholm
    • 4
    • 9
    • 10
  • Vessela N. Kristensen
    • 3
    • 8
  • Jürgen Geisler
    • 3
    • 5
  1. 1.Section of Gene TechnologyAkershus University HospitalLørenskogNorway
  2. 2.Department of PathologyAkershus University HospitalLørenskogNorway
  3. 3.Institute of Clinical MedicineUniversity of OsloLørenskogNorway
  4. 4.Department of Breast and Endocrine SurgeryAkershus University HospitalLørenskogNorway
  5. 5.Department of OncologyAkershus University HospitalLørenskogNorway
  6. 6.Department of Medicine at Solna, Experimental Cardiovascular Research Unit and Departments of Medicine and NeurologyCenter for Molecular Medicine, Karolinska InstituteStockholmSweden
  7. 7.Health Services Research UnitAkershus University HospitalLørenskogNorway
  8. 8.Clinical Molecular Biology (EPIGEN)Akershus University HospitalLørenskogNorway
  9. 9.Norwegian System of Compensation to PatientsOsloNorway
  10. 10.The Norwegian University of Life SciencesÅsNorway

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